Specific gene blockade shows that peptide nucleic acids readily enter neuronal cells in vivo.
Peptide nucleic acids (PNAs) are DNA analogs that can hybridize to complementary sequences with high affinity and stability. Here, we report the first evidence of intracellular delivery of PNAs in vivo. Two CNS receptors, an opioid (mu) and a neurotensin (NTR-1), were targeted independently by repeated microinjection of PNAs into the periaqueductal gray. Behavioral responses to neurotensin (antinociception and hypothermia) and morphine (antinociception) were lost in a specific manner. Binding studies confirmed a large reduction in receptor sites. The loss of behavioral responses was long lasting but did fully recover. The implications of specifically and readily turning off gene expression in vivo are profound.
Tyler
B M
BM
Neuropsychopharmacology, Mayo Clinic, Jacksonville, FL 32224, USA. tyler.beth@mayo.edu
McCormick
D J
DJ
Hoshall
C V
CV
Douglas
C L
CL
Jansen
K
K
Lacy
B W
BW
Cusack
B
B
Richelson
E
E
D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D009020:Morphine / Q000378:metabolism / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism*; D009496:Neurotensin / Q000378:metabolism / Q000494:pharmacology; D009838:Oligodeoxyribonucleotides / Q000378:metabolism* / Q000494:pharmacology; D010455:Peptides / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018028:Receptors, Neurotensin / Q000235:genetics; D011957:Receptors, Opioid / Q000235:genetics
D009838:Oligodeoxyribonucleotides; D010455:Peptides; D018028:Receptors, Neurotensin; D011957:Receptors, Opioid; D009496:Neurotensin; D009020:Morphine